Chlorine adsorption induced structure and energetics change of vinyl chloride physisorbed on Ag(1 1 1)

On the Ag(1 1 1) surface pre-adsorbed with Cl, TDS and HREELS studies find that vinyl chloride physisorbs molecularly with a binding energy 8 kJ/mol stronger and an adsorption geometry more parallel to the surface in comparison with adsorption on clean Ag(1 1 1). The vinyl chloride in close proximity to the surface Cl has stronger binding energy than the ones further removed from Cl. The binding energy change due to surface Cl can be modeled with charge-dipole interaction between the negatively charged Cl and the large molecular dipole of vinyl chloride

Id2 complexes with the SNAG domain of Snai1 inhibiting Snai1-mediated repression of integrin beta4

The epithelial-mesenchymal transition (EMT) is a fundamental process that underlies development and cancer. Although the EMT involves alterations in the expression of specific integrins that mediate stable adhesion to the basement membrane, such as alpha6beta4, the mechanisms involved are poorly understood. Here, we report that Snai1 inhibits beta4 transcription by increasing repressive histone modification (trimethylation of histone H3 at K27 [H3K27Me3]). Surprisingly, Snai1 is expressed and localized in the nucleus in epithelial cells, but it does not repress beta4. We resolved this paradox by discovering that Id2 complexes with the SNAG domain of Snai1 on the beta4 promoter and constrains the repressive function of Snai1. Disruption of the complex by depleting Id2 resulted in Snai1-mediated beta4 repression with a concomitant increase in H3K27Me3 modification on the beta4 promoter. These findings establish a novel function for Id2 in regulating Snai1 that has significant implications for the regulation of epithelial gene expression

Neuropilin-2 promotes branching morphogenesis in the mouse mammary gland

Although the neuropilins were characterized as semaphorin receptors that regulate axon guidance, they also function as vascular endothelial growth factor (VEGF) receptors and contribute to the development of other tissues. Here, we assessed the role of NRP2 in mouse mammary gland development based on our observation that NRP2 is expressed preferentially in the terminal end buds of developing glands. A floxed NRP2 mouse was bred with an MMTV-Cre strain to generate a mammary gland-specific knockout of NRP2. MMTV-Cre;NRP2(loxP/loxP) mice exhibited significant defects in branching morphogenesis and ductal outgrowth compared with either littermate MMTV-Cre;NRP2(+/loxP) or MMTV-Cre mice. Mechanistic insight into this morphological defect was obtained from a mouse mammary cell line in which we observed that VEGF(165), an NRP2 ligand, induces branching morphogenesis in 3D cultures and that branching is dependent upon NRP2 as shown using shRNAs and a function-blocking antibody. Epithelial cells in the mouse mammary gland express VEGF, supporting the hypothesis that this NRP2 ligand contributes to mammary gland morphogenesis. Importantly, we demonstrate that VEGF and NRP2 activate focal adhesion kinase (FAK) and promote FAK-dependent branching morphogenesis in vitro. The significance of this mechanism is substantiated by our finding that FAK activation is diminished significantly in developing MMTV-Cre;NRP2(loxP/loxP) mammary glands compared with control glands. Together, our data reveal a VEGF/NRP2/FAK signaling axis that is important for branching morphogenesis and mammary gland development. In a broader context, our data support an emerging hypothesis that directional outgrowth and branching morphogenesis in a variety of tissues are influenced by signals that were identified initially for their role in axon guidance

Evaluating Differences in the Active-Site Electronics of Supported Au Nanoparticle Catalysts Using Hammett and DFT Studies

Supported metal catalysts, which are composed of metal nanoparticles dispersed on metal oxides or other high-surface-area materials, are ubiquitous in industrially catalysed reactions. Identifying and characterizing the catalytic active sites on these materials still remains a substantial challenge, even though it is required to guide rational design of practical heterogeneous catalysts. Metal-support interactions have an enormous impact on the chemistry of the catalytic active site and can determine the optimum support for a reaction; however, few direct probes of these interactions are available. Here we show how benzyl alcohol oxidation Hammett studies can be used to characterize differences in the catalytic activity of Au nanoparticles hosted on various metal-oxide supports. We combine reactivity analysis with density functional theory calculations to demonstrate that the slope of experimental Hammett plots is affected by electron donation from the underlying oxide support to the Au particles

Regulated splicing of the alpha6 integrin cytoplasmic domain determines the fate of breast cancer stem cells

Although the alpha6beta1 integrin has been implicated in the function of breast and other cancer stem cells (CSCs), little is known about its regulation and relationship to mechanisms involved in the genesis of CSCs. We report that a CD44(high)/CD24(low) population, enriched for CSCs, is comprised of distinct epithelial and mesenchymal populations that differ in expression of the two alpha6 cytoplasmic domain splice variants: alpha6A and alpha6B. alpha6Bbeta1 expression defines the mesenchymal population and is necessary for CSC function, a function that cannot be executed by alpha6A integrins. The generation of alpha6Bbeta1 is tightly controlled and occurs as a consequence of an autocrine vascular endothelial growth factor (VEGF) signaling that culminates in the transcriptional repression of a key RNA-splicing factor. These data alter our understanding of how alpha6beta1 contributes to breast cancer, and they resolve ambiguities regarding the use of total alpha6 (CD49f) expression as a biomarker for CSCs

Invariant Forms and Automorphisms of Locally Homogeneous Multisymplectic Manifolds

It is shown that the geometry of locally homogeneous multisymplectic manifolds (that is, smooth manifolds equipped with a closed nondegenerate form of degree > 1, which is locally homogeneous of degree k with respect to a local Euler field) is characterized by their automorphisms. Thus, locally homogeneous multisymplectic manifolds extend the family of classical geometries possessing a similar property: symplectic, volume and contact. The proof of the first result relies on the characterization of invariant differential forms with respect to the graded Lie algebra of infinitesimal automorphisms, and on the study of the local properties of Hamiltonian vector fields on locally multisymplectic manifolds. In particular it is proved that the group of multisymplectic diffeomorphisms acts (strongly locally) transitively on the manifold. It is also shown that the graded Lie algebra of infinitesimal automorphisms of a locally homogeneous multisymplectic manifold characterizes their multisymplectic diffeomorphisms.Comment: 25 p.; LaTeX file. The paper has been partially rewritten. Some terminology has been changed. The proof of some theorems and lemmas have been revised. The title and the abstract are slightly modified. An appendix is added. The bibliography is update

The SME paradox? Investigating ill-treatment behaviours in small and medium-sized enterprises in Ireland

This is the author accepted manuscript. The final version is available from SAGE Publications via the DOI in this recordThe dynamics of employment relations in small and medium-sized enterprises (SMEs) have attracted academic interest since the 1970s. To date, research debates have converged around two competing perspectives extolling either the opportunities, or the exploitation caused by informal working practices in smaller sized firms. Responding to calls for a more balanced and nuanced view, we analyse n = 1764 responses from a nationally representative study of workplace relations in Ireland, specifically focusing on negative behaviours in SMEs. We contribute to bullying and SME literatures by disaggregating the SME label and showing that certain employee groups in medium-sized firms are likely to report higher incidences of ill-treatment than their counterparts in smaller and larger firms. We conclude by making recommendations on how managers, owners and HRM practitioners can use our study’s findings to improve employee experiences and tackle bullying, harassment and other types of ill-treatment in their respective working environments

Irish workplace behaviour study

This study replicated the BWBS in Ireland, employing the same questionnaire and sampling methodology, in order to establish the prevalence of negative acts in the workplace in a nationally representative sample of Irish employees. The focus of the study is workplace ill treatment received at least once over the previous two years. Workplace ill treatment takes many forms. Workplace bullying is perhaps the most well researched aspect of workplace ill treatment, and has become the dominant way of conceptualising trouble at work. Workplace bullying is a problem for practitioners, academics, and most significantly, it is a problem for those who experience or witness it. There is incontrovertible evidence that ill treatment, impacts negatively on worker health. Many studies cumulatively attest to the toxic effects of ill treatment in work on both physical and mental health and well being. Despite this, ill treatment remains prevalent in workplaces in many countries and organisational response is typically poor. I n 20011 and 20072, national surveys on workplace bullying were conducted in Ireland. These studies found prevalence rates of 7% and 7.9% respectively, employing a self labelling method, in which respondents were asked, following the presentation of a definition, to state whether or not they have been bullied in the past six months. A number of contextual factors make a new survey timely. The British Workplace Behaviour Survey (BWBS) was administered by face-to-face structured interview to a representative sample of UK employees between 2007 and 2008, gathering data on demographic factors, job and workplace characteristics, respondents’ views about their levels of control over the pace and nature of their work, and about why people think they are ill-treated in their workplaces. The survey employed a behavioural checklist, amended following cognitive testing, and including eight items on ‘unreasonable management’, 11 items measuring ‘incivility and disrespect’ and two items on ‘physical violence’. The cognitive testing element was critical to improving the validity of the instrument, and minimised the possibility of errors in conceptualisation and interpretation of items. Respondents were also asked if they had witnessed or perpetrated any of the 21 items

GLI1 regulates a novel neuropilin-2/alpha6beta1 integrin based autocrine pathway that contributes to breast cancer initiation

The characterization of cells with tumour initiating potential is significant for advancing our understanding of cancer and improving therapy. Aggressive, triple-negative breast cancers (TNBCs) are enriched for tumour-initiating cells (TICs). We investigated that hypothesis that VEGF receptors expressed on TNBC cells mediate autocrine signalling that contributes to tumour initiation. We discovered the VEGF receptor neuropilin-2 (NRP2) is expressed preferentially on TICs, involved in the genesis of TNBCs and necessary for tumour initiation. The mechanism by which NRP2 signalling promotes tumour initiation involves stimulation of the alpha6beta1 integrin, focal adhesion kinase-mediated activation of Ras/MEK signalling and consequent expression of the Hedgehog effector GLI1. GLI1 also induces BMI-1, a key stem cell factor, and it enhances NRP2 expression and the function of alpha6beta1, establishing an autocrine loop. NRP2 can be targeted in vivo to retard tumour initiation. These findings reveal a novel autocrine pathway involving VEGF/NRP2, alpha6beta1 and GLI1 that contributes to the initiation of TNBC. They also support the feasibility of NRP2-based therapy for the treatment of TNBC that targets and impedes the function of TICs. of EMBO

A laminin 511 matrix is regulated by TAZ and functions as the ligand for the alpha6Bbeta1 integrin to sustain breast cancer stem cells

Understanding how the extracellular matrix impacts the function of cancer stem cells (CSCs) is a significant but poorly understood problem. We report that breast CSCs produce a laminin (LM) 511 matrix that promotes self-renewal and tumor initiation by engaging the alpha6Bbeta1 integrin and activating the Hippo transducer TAZ. Although TAZ is important for the function of breast CSCs, the mechanism is unknown. We observed that TAZ regulates the transcription of the alpha5 subunit of LM511 and the formation of a LM511 matrix. These data establish a positive feedback loop involving TAZ and LM511 that contributes to stemness in breast cancer